Bioflavonoids have a similar chemical structure to etoposide, the well-characterized topoisomerase II (Top2) poison, and evidence shows that they also induce DNA double-strand breaks (DSBs) and promote genome rearrangements. The purpose of this study was to determine the kinetics of bioflavonoid-induced DSB appearance and repair, and their dependence on Top2. Cells were exposed to bioflavonoids individually or in combination in the presence or absence of the Top2 catalytic inhibitor dexrazoxane. The kinetics of appearance and repair of γH2AX foci were measured. In addition, the frequency of resultant MLL-AF9 breakpoint cluster region translocations was determined. Bioflavonoids readily induced the appearance of γH2AX foci, but bioflavonoid combinations did not act additively or synergistically to promote DSBs. Myricetininduced DSBs were mostly reduced by dexrazoxane, while genistein and quercetin-induced DSBs were only partially, but significantly, reduced. By contrast, luteolin and kaempferol-induced DSBs increased with dexrazoxane pre-treatment. Sensitivity to Top2 inhibition correlated with a significant reduction of bioflavonoid-induced MLL-AF9 translocations. These data demonstrate that myricetin, genistein, and quercetin act most similar to etoposide although with varying Top2dependence. By contrast, luteolin and kaempferol have distinct kinetics that are mostly Top2independent. These findings have implications for understanding the mechanisms of bioflavonoid activity and the potential of individual bioflavonoids to promote chromosomal translocations. Further, they provide direct evidence that specific Top2 inhibitors or targeted drugs could be developed that possess less leukemic potential or suppress chromosomal translocations associated with therapy-related and infant leukemias.
Background Decolonization (decol) and environmental cleaning are strategies to reduce MDRO transmission and infection. While decol in NHs has been proven to reduce MDRO carriage, infection-related hospitalization, and contamination, the impact of enhanced cleaning (EC) with or without decol has not been evaluated. Methods We performed a 4-phase study in 2 NHs from 2019–21 to compare 1) decol, 2) EC, and 3) decol plus EC on MDRO carriage and contamination vs routine care (control). Decol involved nasal iodophor on admission x 5d and then M-F biweekly plus chlorhexidine for routine bathing for all residents. EC involved standardized training for cart setup, disinfectant preparation and saturation, color-coded microfiber cloths for specific items, and UV marker feedback. Outcomes were serial MDRO point prevalence (6 per phase) of nares/skin and MDRO contamination of high-touch bedroom and common area objects. Swabs were processed for MRSA, VRE, ESBL, and CRE. We used generalized linear mixed models to compare phases while clustering by NH. Analyses of objects also clustered by room. Results Table 1 shows crude MDRO prevalence and environmental contamination by study phase. Table 2 shows the impact of each phase vs control. Decol had the greatest impact on MDRO carriage with a 46% reduction vs control. EC alone did not decrease MDRO carriage, and EC plus decol did not further reduce MDRO carriage vs decol alone. The impact of decol vs EC on carriage differed for Gram-positive (GP) vs negative (GN) pathogens. Only decol reduced MRSA and VRE carriage, while both decol and EC reduced GN carriage. The reduction in GN carriage was enhanced with both decol and EC, although this was not statistically significant. With EC, 24-hour UV marker removal of high-touch objects increased from 7% to 45%. Decol and EC both reduced MDRO object contamination, by 84% and 75%, respectively. The impact of decol on object contamination was not enhanced with EC. This table shows the crude MDRO prevalence and environmental contamination results by study phase. Each phase involved 6 serial point prevalence sweeps of 40 residents per nursing home (N=480 total residents per phase), and 6 serial sweeps of high-touch bedroom and common area objects (N=504 total objects per phase). This table shows the odds ratios and 95% confidence intervals for any MDRO and specific MDRO-types for each study phase for the outcomes of 1) MDRO body-site prevalence and 2) MDRO contamination of high-touch objects. The P-value reported represents the overall comparison of the intervention study phases versus control (routine care). Conclusion Multimodal strategies are needed to reduce MDRO burden in NHs. While both decolonization and cleaning independently reduced MDRO object contamination, only decolonization significantly reduced MDRO carriage prevalence. Decolonization provided substantial reductions in MDRO carriage and environmental contamination compared to cleaning alone. Disclosures Gabrielle M. Gussin, MS, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Raveena D. Singh, MA, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Raheeb Saavedra, AS, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Susan S. Huang, MD, MPH, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products|Molnlyke: Conducted clinical studies in which hospitals received contributed antiseptic product|Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products|Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic product.
Background OC is the 6th largest U.S. county with 70 NHs. Universal decolonization (chlorhexidine for routine bathing, and twice daily nasal iodophor Mon-Fri every other week) was adopted in 24 NHs prior to the COVID-19 pandemic, and 12 NHs (11 of those adopting decolonization) participated in a COVID prevention training program with a rolling launch from July-Sept 2020. We evaluated the impact of these initiatives on staff and resident COVID cases. Methods We conducted a quasi-experimental study of the impact of decolonization and COVID prevention training on staff and resident COVID cases during the CA winter surge (11/16/20-1/31/21), when compared to non-participating NHs. Decolonization NHs received weekly visits for encouraging adherence during the pandemic, and NHs in the COVID training program received 3 in-person training sessions for all work shifts plus weekly feedback about adherence to hand hygiene, masking, and breakroom safety using video monitoring. We calculated incident 1) staff COVID cases, 2) resident COVID cases, and 3) resident COVID deaths adjusting for NH average daily census. We assessed impact of initiatives on these outcomes using linear mixed effects models testing the interaction between any training participation and calendar date when clustering by NH. Because of the overlap of the two initiatives, we evaluated ‘any training’ vs ‘no training.’ Results 63 NHs had available data. 24 adopted universal decolonization, 12 received COVID training (11 of which participated in decolonization), and 38 were not enrolled in either. During the winter surge, the 63 NHs experienced 1867 staff COVID cases, 2186 resident COVID cases, and 251 resident deaths due to COVID, corresponding to 29.6, 34.7, and 4.0 events per NH, respectively. In NHs participating in either initiative, staff COVID cases were reduced by 31% (OR=0.69 (0.52, 0.92), P=0.01), resident COVID cases were reduced by 43% (OR=0.57 (0.39, 0.82), P=0.003), and resident deaths were reduced (non-significantly) by 26% (OR=0.74 (0.46, 1.21), P=0.23). The grey box represents the California COVID-19 winter surge (11/16/20-1/31/21). Incident and cumulative COVID-19 cases and deaths for each nursing home were divided by the nursing home’s average daily census and multiplied by 100, representing events per 100 beds, which were aggregated across groups. Conclusion NHs are vulnerable to COVID-19 outbreaks. A universal decolonization and COVID prevention training initiative in OC, CA significantly reduced staff and resident COVID cases in this high-risk care setting. Disclosures Gabrielle Gussin, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Raveena Singh, MA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Raheeb Saavedra, AS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Robert Pedroza, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Chase Berman, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.